Glutamic acid is a neurotransmitter mediating excitatory transmission in central nervous system. Glutamic acid is related to various important brain function such as life and death, differentiation and proliferation of neuron; development of neuron and glial cells, flexible change of neurotransmission efficiency of mature or developed brain, as well as various neurotransmission (see for example, Annual Review of Biophysics and Biomolecular Structure, Vol. 23, p. 319 (1994), etc.).
From pharmacological and molecular biological studies, glutamate receptors in mammal's central nervous system are classified into two classes, i.e. ion channel-glutamate receptor, and metabotropic glutamate receptor (hereinafter referred to as “mGluR”). Ion channel-glutamate receptors are comprised of a complex of different subunit proteins, and are ion channels gating with the bindings of ligands. On the other hand, mGluR conjugates with GTP binding protein, and acts by controlling production of intracellular second messengers, or activation of ion channel via GTP binding protein (see for example, Brain Research Reviews, Vol. 26, p. 230 (1998), etc.).
From studies so far, mGluR has been reported to exist as eight different subtypes of mGluR1 to MGluR8. These subtypes are classified into three subgroups based on homology of amino acid sequence, signaling, and pharmacological properties. Group I (mGluR 1 and 5) activates phospholipase C against intracellular signaling, while Group II (mGluR2 and 3) and Group III (mGluR4, 6, 7 and 8) regulates adenylate cyclase activity to suppress accumulation of cyclic adenosine monophosphate (CAMP) by forskolin stimulation. Moreover, Group II is selectively activated by LY354740 described in for example, Journal of Medicinal Chemistry, Vol. 42, p. 1027 (1999), etc., and Group III is selectively activated by L-AP4. Furthermore, various receptors other than mGluR6 which exists specifically in retina express widely in brain and nervous systems, each showing characteristic distribution within the brain, and each receptor is believed to have a different physiological function (see for example, Neurochemistry International, Vol. 24, p. 439 (1994); European Journal of Pharmacology, Vol. 375, p. 277 (1999), etc.).
Moreover, as for compounds structurally similar to formula (I), for example a compound shown by formula (A):
is described (see for example, WO03/051315, etc.).
The compound shown by the above formula (A) is common to the compound of the present invention on the point that the group bound to the 1st position of triazole group is a phenyl group substituted by a fluorine. However, while the group bound to the 4th position of triazole group of the formula (A) is a pyridyl group, the group bound to the 4th position of triazole ring of the compound (I) of the present invention, is different being a double ring group. Moreover, it is also different as the compound shown by (A) is a modulator of mGluR5, while the compound (I) of the present invention is a compound showing mGluR1 inhibiting effect.